rs1476046

chr6-12292988-G-Achr6-12292988-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001955.5(EDN1):c.233+479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,158 control chromosomes in the GnomAD database, including 3,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3958 hom., cov: 32)
• Consequence: EDN1 NM_001955.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

Genes affected

EDN1 (HGNC:3176): (endothelin 1) This gene encodes a preproprotein that is proteolytically processed to generate a secreted peptide that belongs to the endothelin/sarafotoxin family. This peptide is a potent vasoconstrictor and its cognate receptors are therapeutic targets in the treatment of pulmonary arterial hypertension. Aberrant expression of this gene may promote tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDN1	NM_001955.5	c.233+479G>A		intron_variant		ENST00000379375.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDN1	ENST00000379375.6	c.233+479G>A		intron_variant		1	NM_001955.5	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34176 AN: 152040 Hom.: 3960 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34176 AN: 152158 Hom.: 3958 Cov.: 32 AF XY: 0.228 AC XY: 16927 AN XY: 74386

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.205

Alfa AF: 0.224 Hom.: 641

Bravo AF: 0.220

Asia WGS AF: 0.313 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.72
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1476046; hg19: chr6-12293221;